1,3-Dithiolane compounds and method of preparation thereof

ABSTRACT

There are provided substituted 1,3-dithiolane compounds and a method for preparing the same. Said 1,3-dithiolane compounds are useful intermediates in the preparation of tetrahydro-7-oxobenzo[b]thien-4-ylureas and tetrahydro-4-oxo-1-naphthylureas which are known animal growth-promoting agents, which thiolanes are represented by the formula: ##STR1## wherein R 1  is a member selected from the group consisting of 2-thienyl and phenyl; R 2  is a member selected from the group consisting of ##STR2## wherein X is chlorine or bromine; R 3  and R 4  are each members selected from the group consisting of hydrogen and methyl; and when R 1  and R 2  are taken together with the carbon atom to which they are attached they represent a bicyclic moiety selected from the group consisting of ##STR3## wherein the carbon atom of said bicyclic moiety marked with an asterisk is also part of the 1,3-dithiolane ring; U is a moiety selected from the group consisting of ##STR4## and when U is ##STR5## said compounds are the racemic mixtures and the optical isomers thereof.

This application is a divisional application of Ser. No. 799,887 filedon 5/23/77.

BACKGROUND OF THE INVENTION

The compounds: 4,5,6,7-tetrahydro-7-oxobenzo[b]-thien-4-ylurea offormula (I) and 1,2,3,4-tetrahydro-4-oxo-1-naphthylurea of formula (II):##STR6## wherein R' and R" are substituents, such as hydrogen, alkoxy,alkyl and benzyl are useful and valuable animal growth-promoting agents.The compounds of formula (I) are disclosed in the GermanOffenlegungschrift No. 2,501,788 issued July 7, 1975, and are also thesubject of an application for U.S. Pat., Ser. No. 532,449, filed Dec.13, 1974. Compunds of formula (II) are disclosed in an application forU.S. Pat., Ser. No. 582,559, filed May 20, 1975. Both the GermanOffenlegungshrift and the aforementioned applications are incorporatedherein by reference. ##STR7## wherein said amides are the racemicmixtures and the optically active isomers thereof, are useful andvaluable intermediates for the synthesis of the above urea compoundsrepresented by formulas (I) and (II). In general, the amides of formulas(III) and (IV) are conveniently prepared by oxidation reactions from thecorresponding amides of formulas (V) and (VI) as hereinbelow illustratedin the following manner: ##STR8##

To one equivalent of the amide of formula (V) or (VI) are added from 2to 8 equivalents and, preferably, from 4 to 5 equivalents of anoxidizing agent, such as a ceric salt, chromic acid, sodium bichromateand equivalents thereof, at a temperature between about 0° and 100° Cand, preferably, from 20° to 60° C, in an inert solvent such as anaqueous solution of acetic acid, acetonitrile, tetrahydrofuran, dioxane,dimethoxyethane and the like, which can be admixed with nitric acid,phosphoric acid, perchloric acid.

Alternatively, the amides can initially be treated with an oxidizingagent such as chromic anhydride in acetic anhydride, followed byhydrolysis. Further the amides (V) and (VI) can also be oxidized withoxygen or with a mixture of oxygen and an inert gas at atmospheric orsuperatmospheric pressures in the presence of a cobalt catalyst selectedfrom any suitable Co⁺² and Co⁺³ salt, in a solvent selected from loweralkanoic acids, aliphatic or cycloaliphatic ketones, lower alcohols, ormixtures thereof, at a temperature range of 20° to 150° C, andpreferably 25° to 120° C.

Each of the above procedures affords desired intermediates [formulas(III) and (IV)] in satisfactory yields. However, the use of metaloxidizing agents is expensive and their recovery from an oxidizingmixture is difficult. Moreover, the use of an oxidant, such as chromicacid in acetic anhydride, can result in the formation of chromylacetate, a potentially explosive compound. The oxygen/catalyst routealso poses a problem, since it employs flammable solvents, some of which(the ketones) may form potentially dangerous peroxides.

Thus, disposal of the effluents, containing the above oxidants, in theenvironment can have an undesired impact on same, the magnitude of whichcan not be predicted with any degree of certainty.

It is apparent, therefore, that is a procedure which does not requireany oxidation reactions for the preparation of compounds of formulas(III) and (IV) could be devised, such would fulfil a long felt need inthe art.

Surprisingly, it has been found that the compounds of the presentinvention represented by formulae (VII or VIII) are provided which canbe converted with ease to the corresponding compounds of formulas (III)and (IV) as hereinbelow graphically illustrated: ##STR9## wherein R₃ andR₄ are each hydrogen or methyl; as well as the racemic mixtures and theoptical isomers thereof.

Hydrolysis of the amides of formulas (III) and (IV) yields thecorresponding oxo amines of formula (IX) and (X): ##STR10## which, whenreacted with urea, metal cyanates, alkyl or aryl isocyanates, carbamoylhalides, yield the afore-said animal growth regulating compounds offormulas (I) and (II).

According to the invention, the 1,3-dithiolane compounds are representedby formula (XI) below: ##STR11## wherein R₁ is a member selected fromthe group consisting of 2-thienyl and phenyl; R₂ is a member selectedfrom the group consisting of ##STR12## wherein X is chlorine or bromine;R₃ and R₄ are each members selected from the group consisting ofhydrogen and methyl; and when R₁ and R₂ are taken together with thecarbon atom to which they are attached they represent a bicyclic moietyselected from the group consisting of ##STR13## wherein the carbon atomof said bicyclic moiety marked with an asterisk is also part of the1,3-dithiolane ring; U is a moiety selected from the group consisting of##STR14## and when U is ##STR15## said compounds are the racemicmixtures and the optical isomers thereof.

The reaction sequence leading to the compounds (XI) of the presentinvention is hereinbelow graphically illustrated by flow diagrams,wherein R₁ of formula (XI) hereinabove is either 2-thienyl or phenyl asindicated in Scheme 1. or Scheme 2, respectively. ##STR16##

Advantageously, the 1,3-dithiolanes of formula (XI) can alternatively beprepared by the following reaction sequence: ##STR17##

Thiophene (a) is reacted with succinic anhydride (c) underFriedel-Crafts reaction conditions to afford 4-(2-thienyl)-4-oxobutyricacid (XII). Substitution of benzene (b) in the above reaction affords4-phenyl-4-oxobutyric acid (XVII). ##STR18## The oxobutyric acids offormulas (XII) and (XVII) obtained in Step 1 above, are reacted with asuitable 1,2-dithiol (d), R₃ and R₄ are each either hydrogen or methyl,in an aromatic solvent such as benzene, toluene or xylene, in thepresence of catalytic amounts of p-toluenesulfonic acid at a temperaturerange of 25° to 120° C and, preferably, from 75° to 110° C whileazeotroping the water formed in the reaction. Alternatively, thereaction is conducted in a C₂ -C₅ alkanoic acid, preferably, acetic acidin the presence of an acid catalyst such as boron trifluoride/methanol,boron trifluoride/ether, ZnCl₂ /Na₂ SO₄, HCl/ether, and the like, at thetemperature range specified above, to afford2-(2-thienyl)-1,3-dithiolanepropionic acid (XIII) and2-phenyl-1,3-dithiolane-2-propionic acid (XVIII), respectively. R₃ andR₄ are as hereinabove defined. ##STR19## The dithiolane propionic acidsof formulae (IIIa) and (IIIb) are converted to the corresponding acidchlorides of formulae (XIV) and (XIX) with oxalyl chloride or thionylchloride (with a small amount of DMF added if desired) in an inertanhydrous solvent selected from the group consisting of benzene,toluene, xylene, chlorobenzene, at a temperature range of about 0° to30° C and preferably 15° to 30° C. ##STR20##

In this reaction step, the acid chlorides of formulae (XIV) and (XIX)are ring closed with stannic chloride in an inert anhydrous solvent suchas methylene chloride, ethylene dichloride and the like, at atemperature range of -20° to +20° C preferably 0° to 10° C, to affordspiro[benzo[b]thiophene-7(6H), 2'-[1,3]dithiolan]-4(5H)-one of formula(XV) and spiro[naphthalene-4(3H), 2'-[1,3]dithiolan]-1(2H)-one offormula (XX), respectively, or derivatives thereof wherein R₃ and R₄ areeach hydrogen or methyl. ##STR21## Conversion of the oxo compounds offormulae (XV) and (XX) to the corresponding formamides is achieved byheating same with an equimolar or excess amount of formamide-formic acidor ammonium formate-formic acid mixture at a temperature of about 150°to 200° C and preferably 150° to 180° C for a period of time about 3 to8 hours to afford N-(5,6-dihydrospiro[benzo[b]thiophen-7(6H),2'-[1,3-dithiolan]-4-yl)formamide of formula (XVI) andN-(2,3-dihydrospiro[naphthalene-4(3H), 2'-[1,3-dithiolan]-4-yl)formamideof formula (XXI), respectively, wherein said compounds are the racemmicmixtures and the optical isomers thereof.

The removal of the 1,3-dithiolane group and the simultaneousintroduction of an oxo group on the same carbon atom in the compounds offormulae (XVI) and (XXI) is readily accomplished by using mercurichalide, such as mercuric chloride/aqueous calcium carbonate inacetonitrile or acetone, at a temperature range of 20° to 70° C,preferably 20° to 40° C to afford the compounds of formulae (III) and(IV) as hereinbelow graphically illustrated: ##STR22##

Next, the amides of formulae (III) and (IV) are hydrolyzed with diluteacid or alkali, preferably an acid (e.g. hydrochloric acid) to4,5,6,7-tetrahydro-7-oxobenzo[b]thiophen-4-amine of formula (IX) and1,2,3,4-tetrahydro-4-oxo-1-naphthylamine of formula (X), or saltsthereof, as hereinbelow graphically illustrated: ##STR23## and whereinsaid oxoamines are the racemic mixtures and the optical isomers thereof.

Formulas (I) and (II) urea compunds, wherein R' and R" are hydrogen, maybe advantageously prepared from the above-identified oxoamines (or acidsalts thereof) by reacting said amines with approximately equimolaramounts of sodium or potassium cyanate, however it is generallypreferable to employ 5 to 50% excess of the cyanate.

The reaction can be conducted at atmospheric or superatmosphericpressure at a temperature in the range of 0° to 100° C, but ispreferably conducted at atmospheric pressure at 0° to 70° C in thepresence of a solvent selected from water, polar solvents such as C₁ -C₃alcohols, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether,acetone, methyl ethyl ketone and the like, and mixtures thereof; in thepH range of 5 to 7 and preferably at pH 6. The above reaction may begraphically illustrated as follows: ##STR24##

Substituted ureas of formulae (I) or (II) may be advantageously preparedby treating the above-identified amines of formulae (IX) or (X) with anappropriately substituted alkyl isocyanate of formula: R'--NCO or with acarbamoyl halide of formula: ##STR25## halide, wherein R' and R" are ashereinabove defined and halide may be chloro or bromo. The free bases of(IX) or (X) may be employed or acid addition salts thereof, preferablythe hydrochloride, in the presence of an acid acceptor. Suitable acidacceptors may be pyridine, triethylamine (or any suitable tertiaryamine), alkali metal carbonates such as potassium carbonate and sodiumcarbonate, strong basic ion-exchange resins, and aqueous alkali. Thereaction may be run from about 0° to 100° C, and, preferably, at 0° to70° C until the desired reaction is complete. The isocyanate orcarbamoyl halide is generally used in equimolar amounts but it may beused in excess.

Suitable organic solvents for the above reactions include aproticaromatic solvents such as benzene, toluene and xylene; chlorinatedhydrocarbon solvents such as methylene chloride, chloroform anddichloroethane; ethers such as tetrahydrofuran, diethyl ether,dimethoxyethane, diethylene glycol dimethyl ether and dioxane; ketonessuch as acetone, methyl ethyl ketone, methyl butyl ketone, methylisobutyl ketone; or mixtures of said solvents. The above reactions maybe graphically illustrated as follows: ##STR26## wherein R' and R" areas hereinabove defined.

All of the hereinbefore described preparations of4,5,6,7-tetrahydro-7-oxobenzo[b]thiophene-, and1,2,3,4-tetrahydro-4-oxonaphthalene derivatives yield racemic (dl)mixtures. Should the optically active isomers of the above compounds bedesired, these may be obtained by the resolution of the racemic (dl)formulae (IX) and (X) compounds, and using the thus obtained opticallyactive isomers in subsequent reactions.

As stated above, formulae (I) and (II) compounds are useful asgrowth-promoting agents for animals such as poultry, fur-bearing andfarm animals, and the use of said compounds for this purpose providesthe added advantage of improving feed conversion for said animals. Theterm "feed conversion" means the ratio of unit weight of feed per unitweight of gain and improvement in feed conversion means increased weightgain from a given unit of feed consumed.

A growth-promoting amount of a formula (I) or a formula (II) compound oran optically active isomers thereof is administered to a host animal in,or with, the animal's feed. Said compound may also be administered as asubcutaneous implant under the skin of said animal or as a parenteralinjection. When administered in the feed of said animals, usually about0.0001 to about 0.08% by weight, and preferably 0.001 to 0.04% by weightof formula (I) or formula (II) urea, is effective for increasing growthrate and improving feed conversion. When administered as a parenteralinjection or subcutaneous implant, usually in amounts that will supplyabout 0.0005 mg to about 0.2 mg, preferably 0.001 mg to 0.1 mg/kg ofbody weight per day of the active compound, it will produce the desiredimprovement in weight gain and enhance feed conversion.

The invention is further illustrated by the non-limiting examples setforth below.

EXAMPLE 1 Preparation of 2-(2-thienyl)-1,3-dithiolane-2-propionic acid

Ethanedithiol (18.8 ml) is added to a stirred solution of4-(2-thienyl)-4-oxobutyric acid (18.4 g) in 100 ml of 1% BF₃ -methanolin acetic acid. The mixture is stirred for 2 days in an oil bath kept at110° to 120° C. The mixture is then poured on ice, stirred for 1 hour,and is filtered. The filter cake is washed with water (400 ml), and isdried. The dry filter cake is dissolved in methylene chloride (200 ml)and the solution dried over magnesium sulfate. The solution is thenfiltered and evaporated to dryness in vacuo to afford 25.1 g of titlecompound. Recrystallization from a methylene chloride - hexane mixtureaffords 18.8 g of title compound, m.p. 55° to 64° C.

Similarly, substitution of 1,2-propanedithiol in place of ethanedithiolaffords 4-methyl-2-(2-thienyl)-1,3-dithiolane-2-propionic acid. The useof 2,3-butanedithiol affords4,5-dimethyl-2-(2-thienyl)-1,3-dithiolane-2-propionic acid,respectively.

In the same manner, 4-phenyl-4-oxobutyric acid is converted to2-phenyl-1,3-dithiolane-2-propionic acid using ethanedithiol; while theuse of 1,2-propanedithiol and 2,3-butanedithiol affords 4-methyl- and4,5-dimethyl-2-phenyl-1,3-dithiolane-2-propionic acid, respectively.

EXAMPLE 2 Preparation of Spiro[benzo[b]thiophen-7(6H),2'-[1,3]dithiolan]-4(5H)-one

Oxalyl chloride (2.54 g, 1.7 ml., 0.02 mole) is added to a stirredsolution of 2-(2-thienyl)-1,3-dithiolane-2-propionic acid (3.5 g, 0.0135mole) in dry benzene (175 ml) under a nitrogen atmosphere. The solutionis stirred at room temperature for 5.25 hours and is then evaporated todryness to yield the acid chloride as a gold oil. The infrared spectrumexhibits absorption at 1785 cm⁻¹.

The above acid chloride is dissolved in dry methylene chloride (175 ml)and the solution added over a period of 1.3 hours, under a nitrogenatmosphere, at 4° C to a stirred solution of stannic chloride (7.02 g,3.15 ml, 0.027 mole) in dry methylene chloride (350 ml), whilemaintaining the temperature in an ice bath. After the addition iscompleted, the reaction mixture is stirred for 25 minutes then ice andwater (ca 300 ml) are added and the mixture stirred for 30 minutes. Theorganic phase is separated, washed with water, aqueous sodium carbonatesolution, water and saturated salt solution. The organic solution isthen dried over magnesium sulfate and evaporated to dryness to afford2.8 g of title compound as an oily solid. The infrared spectrum exhibitsabsorption at 1655 cm⁻¹ and the nmr spectrum shows two aromatic doubletsat 7.13 δ and 7.27 δ (J = 5.5 Hz).

Under the same conditions, thionyl chloride and a trace of DMF in placeof oxalyl chloride also gives the title compound after cyclization.

In the same manner, 4-methyl-2-(2-thienyl)-1,3-dithiolane-2-propionicacid and 4,5-dimethyl-2-(2-thienyl)-1,3-dithiolane-2-propionic acid areconverted to spiro[benzo-b]thiophene-7(6H),4'-methyl-2'-[1,3]dithiolan]-4[5H]-one andspiro[benzo[b]thiophene-7(6H),4',5'-dimethyl-2'-[1,3]-dithiolan]-4[5H]-one, respectively.

Also in the same manner, spiro[naphthalene-4(3H),2'-[1,3]dithiolan]-1(2H)-one, spiro[naphthalene-4(3H),4'-methyl-2'[1,3]dithiolan]-1(2H)-one and spiro[naphthalene-4(3H),4',5'-dimethyl-2'-[1,3-dithiolan]-1(2H)-one are prepared from theircorresponding 2-phenyl-1,3-dithiolane-2-propionic acids.

EXAMPLE 3 Preparation of N-(5,6-dihydrospiro[benzo[b]thiophen-7(4H),2'-[1,3]dithiolan]-4-yl)formamide

A mixture of spiro[benzo[b]thiophene-7(6H), 2'-[1,3-dithiolan]-4(5H)-one(2.8 g), 98% formamide (4.8 ml) and formic acid (2.26 ml) is stirred andheated overnight in an oil bath kept at 130° C to 140° C. The reactionmixture is poured into water and extracted with chloroform (100 ml). Thechloroform extract is washed with water and saturated salt solution anddried over magnesium sulfate. The solution is then evaporated to drynessto afford 2.6 g of red-black oil. The oil is stirred with methanol (125ml), the supernatant is decanted and evaporated to dryness to afford 1.5g of crude title formamide as an orange oil.

Similarly, spiro[benzo[b]thiophene-7(6H),4'-methyl-2'-[1,3]dithiolan]-4[5H]-one is converted toN-(5,6-dihydrospiro[benzo[b]thiophene-7(4H),4'-methyl-2'-[1,3]dithiolan]-4-yl)formamide, whilespiro[benzo[b]thiophene-7(6H),4',5'-dimethyl-2'-[1,3]dithiolan]-4[5H]-one is converted toN-(5,6-dihydrospiro[benzo[b]thiophene-7(4H),4',5'-dimethyl-2'[1,3]dithiolan]-4-yl)formamide.

Substitution of the corresponding 1,2,3,4-tetrahydronaphtahlenecompounds instead of the above-mentioned benzo[b]thiophene compoundsafford N-(2,3-dihydrospiro-[naphthalene-4(3H),2'-[1,3]dithiolan]-4-yl)formamide,N-(2,3-dihydrospiro[naphthalene-4(3H), 4'-methyl2'-[1,3]-dithiolan]-4-yl)formamide andN-(2,3-dihydrospiro[naphthalene-4(3H),4',5'-dimethyl-2'-[1,3]dithiolan]-4-yl)formamide.

EXAMPLE 4 Preparation ofN-(4,5,6,7-tetrahydro-7-oxobenzo[b]thien-4-yl)-formamide

To a stirred mixture of N-(5,6-dihydrospiro[benzo[b]thiophen-7(4H),2'-[1,3]dithiolan]-4-yl)formamide (1.5 g), acetonitrile (20 ml) andwater is added calcium carbonate (1.65 g) and mercuric chloride (3.0 g).The mixture is stirred at room temperature for 35 minutes andacetonitrile is added. The solid is filtered and washed withacetonitrile. The filtrate (100 ml) is evaporated to dryness to affordthe title compound.

Similarly, N-(5,6-dihydrospiro[benzo[b]thiophene-7(4H),4'-methyl-2'-[1,3]dithiolan]-4-yl)formamide andN-(5,6-dihydrospiro[benzo[b]thiophene-7(4H),4',5'-dimethyl-2'-[1,3]dithiolan]-4-yl)formamide are converted to thetitle compound.

Also in the same manner, N-(2,3-dihydrospiro[naphthalene-4(3H),2'-[1,3]dithiolan]-4-yl)formamide,N-(2,3-dihydrospiro[naphthalene-4(3H),4'-methyl-2'[1,3]-dithiolan]-4-yl)formamide andN-(2,3-dihydrospiro)naphthalene-4(3H),4'5'-dimethyl-2'-[1,3]dithiolan]-4-yl)formamide are converted toN-(1,2,3,4-tetrahydro-4-oxo1-naphthyl)formamide.

EXAMPLE 5 Preparation of 4,5,6,7-Tetrahydro-7-oxobenzo[b]thien-4-ylurea

A mixture of the keto-formamide of Example 4, ethyl alcohol (25 ml) and2N hydrochloric acid (25 ml) is heated at reflux for 4 hours. Themixture is filtered and the solid washed with water. The filtrate isevaporated to dryness, the oily residue is dissolved in 50 ml of waterand filtered. To the aqueous solution of the amine hydrochloride isadded a solution of potassium cyanate (1.0 g) in water (5 ml) and themixture stirred at room temperature overnight. The solid is filtered,washed well with water and air dried to afford 0.59 g of4,5,6,7-tetrahydro-7-oxobenzo[b]thien-4-ylurea, m.p. 228° to 230° C(dec).

EXAMPLE 6 Preparation of 1,2,3,4-Tetrahydro-4-oxo-1-naphthylurea

A solution of N-(1,2,3,4-tetrahydro-4-oxo-1-naphthyl)formamide (11.0 g)in a mixture of 95% ethanol (120 ml) and 2N hydrochloric acid (120 ml)is heated at reflux for 3 hours and then stirred at room temperatureovernight. The solution is filtered and concentrated in vacuo to afforda brownish-red solid. About 120 ml of ethanol is added to the solid andthe mixture is then further concentrated in vacuo to yield 11.3 g ofsolid. This solid is added to 60 ml of water and filtered. The insolubleresidue is washed with 16 ml of water, the aqueous fractions arecombined, stirred and a solution of potassium cyanate in 24 ml of wateradded dropwise. The mixture is stirred overnight, the precipitated brownsolid collected and washed with water then with cold methanol to afford10.4 g of title compound, a grayish-brown solid, m.p. 235° to 238° C(dec).

EXAMPLE 7 Mouse Growth Regulant Tests

CFI female mice from Carworth Farm are received when they are six weeksold. They are housed 10 to a cage in air-conditioned rooms (72°-76° F)with automatically controlled lights, 14 hours on and 10 hours off. Thebasal diet used in these studies is Purina Laboratory Chow (seedescription below), which is supplied ad libitum. Water is also allowedad libitum.

Thirteen days after arrival, the mice are weighed in groups of 10 andassigned at random to the different treatments. The concentration of thedifferent compounds in the diet is indicated in the following Table.Twelve days later the mice are weighed again and the experimentterminated. At least three cages (30 mice) of untreated controls areincluded in each test. Test data are provided in Table I below, whereindata are reported as percent weight gain over controls. The following isa description of the diet to which the growth-promoting compounds areadded.

                  DIET                                                            ______________________________________                                        GUARANTEED ANALYSIS                                                           Crude protein not less than                                                                             23.0%                                               Crude fat not less than    4.5%                                               Crude fiber not more than  6.0%                                               Ash not more than          9.0%                                               ______________________________________                                        INGREDIENTS                                                                   Meat and bone meal, dried skimmed milk, wheat germ                            meal, fish meal, animal liver meal, dried beet pulp,                          ground extruded corn, ground oat groats, soybean meal,                        dehydrated alfalfa meal, cane molasses, animal fat                            preserved with BHA, vitamin B.sub.12 supplement, calcium                      pantothenate, choline chloride, folic acid, riboflavin                        supplement, brewers' dried yeast, thiamin, niacin,                            vitamin A supplement, D activated plant sterol,                               vitamin E supplement, calcium carbonate, dicalcium                            phosphate, iodized salt, ferric ammonium citrate,                             iron oxide, manganous oxide, cobalt carbonate, copper                         oxide, zinc oxide.                                                            ______________________________________                                    

                  Table I                                                         ______________________________________                                        Effectiveness of 4,5,6,7-Tetrahydro-7-oxobenzo[b]thien-4-yl-                  urea and 1,2,3,4-Tetrahydro-4-oxo-1-naphthylurea as Animal                    Growth Promoting Agents Reported as Percent Weight Gain                       Over Controls Using Mice as the Test Animal                                   ______________________________________                                                        Rate ppm   % Weight Gain                                        Compound      in Diet    Over Controls                                      ______________________________________                                        4,5,6,7-Tetrahydro-7-oxo-                                                     benzo[b]thien-4-ylurea                                                                        200         117                                               1,2,3,4-Tetrahydro-4-oxo-                                                                      50        35.71                                              1-naphthylurea  100        97.40                                                              200        93.51                                              ______________________________________                                    

We claim
 1. A 1,3-dithiolane compound of formula: ##STR27## wherein R₃and R₄ are each hydrogen or methyl; and U is the substituent ##STR28##said compound is the racemic mixture and the optical isomers thereof. 2.The compound according to claim 1, spiro{benzo[b]thiophen-7(6H),2'-[1,3]dithiolan}-4(5H)-one.
 3. The compound according to claim 1,racemic N-{5,6-dihydrospiro[benzo[b]thiophen-7(4H),2'-[1,3]dithiolan]-4-yl}formamide and the optical isomers thereof.